Binap, (A+-)- → N-[(1S,2S)-2-[(5-Bromo-3-methoxypyridin-2-yl)amino]cyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide

HRID 1750683Notes

Reaction equation

HRID 1750683 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C@H:9]2[CH2:13][CH2:12][CH2:11][C@@H:10]2[NH:14][C:15](=[O:27])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[N:22]2[N:26]=[CH:25][CH:24]=[N:23]2)=[N:6][CH:7]=1.Cl.N[C@H]1CCC[C@@H]1N[C:36](=[O:48])C1C=CC=CC=1N1N=CC=N1.BrC1C=C(OC)C(Cl)=NC=1.CC(C)([O-])C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Br:1][C:2]1[CH:3]=[C:4]([O:48][CH3:36])[C:5]([NH:8][C@H:9]2[CH2:13][CH2:12][CH2:11][C@@H:10]2[NH:14][C:15](=[O:27])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[N:22]2[N:26]=[CH:25][CH:24]=[N:23]2)=[N:6][CH:7]=1

Participants

7

Reactant 5

HCID 634876Binap, (A+-)-HCID 167481085-Bromo-2-chloro-3-methoxypyridine2×HCID 23676156Sodium t-butoxideHCID 118025476N-[(1S,2S)-2-Aminocyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide hydrochloride2×HCID 118308185N-[(1S,2S)-2-[(5-Bromopyridin-2-yl)amino]cyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide

Product 1

HCID 118308051N-[(1S,2S)-2-[(5-Bromo-3-methoxypyridin-2-yl)amino]cyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

Prepared according to the procedure for N-[(1S,2S)-2-[(5-bromopyridin-2-yl)amino]cyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide (Example 118) from N-[(1S,2S)-2-amino cyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide hydrochloride (Intermediate 4; 300 mg, 0.98 mmol) and 5-bromo-2-chloro-3-methoxypyridine (CAS number 286947-03-3; 260 mg, 1.17 mmol) except after heating overnight, to this was then added further 5-bromo-2-chloro-3-methoxypyridine (CAS number 286947-03-3; 260 mg, 1.17 mmol), sodium tert-butoxide (150 mg, 1.56 mmol), BINAP (24 mg, 0.039 mmol) and tris(dibenzylideneacetone)dipalladium(0) (18 mg, 0.019 mmol) and the reaction was heated at 100° C. for 3 hours. The mixture was partitioned between ethyl acetate (10 ml) and water (10 ml). The aqueous layer was further extracted with ethyl acetate (3×10 ml). The combined organics were washed with brine, filtered through a hydrophobic frit and concentrated in vacuo. The crude product was purified by column chromatography (silica, 0-100% ethyl acetate/petrol) to afford the title compound.

Workup

  1. customPrepared
  2. temperatureexcept after heating overnight
  3. customThe mixture was partitioned between ethyl acetate (10 ml) and water (10 ml)
  4. extractionThe aqueous layer was further extracted with ethyl acetate (3×10 ml)
  5. washThe combined organics were washed with brine
  6. filtrationfiltered through a hydrophobic frit
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by column chromatography (silica, 0-100% ethyl acetate/petrol)

Sources & evidence

ORD record
ord-232baa8d90df4c169d2de7b8115b0e6b
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

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